Abstract The NIDA Clinical Trials Network (CTN) offers the ideal platform to evaluate innovative methods, thereby potentiating technology-driven comparative effectiveness trials in a variety of treatment settings. This renewal application builds upon years of success in the Southern Consortium Node (SCN) of the CTN. Since our inception in 2000, we have built and sustained an outstanding team of inter-professional experts in addictions treatment and research, conducted an array of well-managed clinical trials, and disseminated findings through traditional communication channels, such as professional conferences and peer-reviewed publications. We recognize that in order to have meaningful population impact, treatments must be well integrated into healthcare practices and treatment delivery systems. With this renewal, we capitalize on recent successes in conducting clinical trials in a wide range of healthcare settings that make use of new technologically based methods to screen and treat individuals with substance use disorders (SUDs). Acute care management of SUDs within medical settings (i.e. SBIRT strategies to screen, briefly intervene, and refer to treatment) insufficiently addresses the chronic care needs of SUD patients that are so often marked by relapse. We propose a more comprehensive approach, including chronic care management, based on a broader translational view, using novel, technology-driven strategies to improve screening, increase delivery and efficacy of brief interventions, optimize referrals to specialty care, and develop systems to address the chronic relapsing course of many SUDs. We emphasize the exploration of approaches that are not only effective, but also cost-effective, so as to promote adoption into clinical practice settings. We bring to the network a research team with expertise in the integration of substance use screening, intervention delivery, and referral within primary care and other health care settings. Building on existing strengths in addictions research at MUSC, we have assembled a multi-disciplinary team with expertise in addiction treatment, primary care, bioinformatics, mobile health, health care cost analysis and clinical research to focus on the investigation of effective screening and treatment interventions for SUDs in a variety of settings. We are ideally suited to continue as active members of the CTN consortium in exploring efficient and effective ways to integrate addictions treatment into mainstream medical care. In doing so, we will meet new challenges and take advantage of growing opportunities within the changing healthcare system.